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标题：Malignant Melanoma-Derived Exosomes Induce Endothelial Damage and Glial Activation on a Human BBB Chip Model
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作者：Peng Wang ; Yunsong Wu ; Wenwen Chen 等
期刊名称：Biosensors
电子版ISSN：2079-6374
出版年度：2022
卷号：12
期号：2
DOI：10.3390/bios12020089
语种：English
出版社：MDPI Publishing
摘要：Malignant melanoma is a type of highly aggressive tumor, which has a strong ability to metastasize to brain, and 60–70% of patients die from the spread of the tumor into the central nervous system. Exosomes are a type of nano-sized vesicle secreted by most living cells, and accumulated studies have reported that they play crucial roles in brain tumor metastasis, such as breast cancer and lung cancer. However, it is unclear whether exosomes also participate in the brain metastasis of malignant melanoma. Here, we established a human blood–brain barrier (BBB) model by co-culturing human brain microvascular endothelial cells, astrocytes and microglial cells under a biomimetic condition, and used this model to explore the potential roles of exosomes derived from malignant melanoma in modulating BBB integrity. Our findings showed that malignant melanoma-derived exosomes disrupted BBB integrity and induced glial activation on the BBB chip. Transcriptome analyses revealed dys-regulation of autophagy and immune responses following tumor exosome treatment. These studies indicated malignant melanoma cells might modulate BBB integrity via exosomes, and verified the feasibility of a BBB chip as an ideal platform for studies of brain metastasis of tumors in vitro.
关键词：enblood–brain barrier (BBB)organ chipbrain metastasismalignant melanomaexosomes